iPS cells and renal pharmacological target

抄録

Chronic kidney disease (CKD) causes both medical and medicoeconomical problems worldwide. Regenerative medicine strategies using human pluripotent stem cells, such as human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), are expected as candidates to solve these problems. Cell replacement therapy, disease modeling and drug discovery with patient-derived stem cells should be applied for CKD. However, the methods to generate fully differentiated renal cells and tissues from hiPSCs/ESCs remain to be developed. The mechanisms of kidney morphogenesis and cell fate determination of renal lineage cells have been elucidated by experimental animal models. By mimicking in vivo kidney development, we are aiming to develop stepwise differentiation methods towards adult renal cells and tissues from hiPSCs/ESCs. The mammalian adult kidney, metanephros, develops by mutual interaction between two renal progenitor tissues, the ureteric bud (UB) and metanephric mesenchyme (MM) that are derived from early embryonic germ layers, anterior and posterior intermediate mesoderms (IMs), respectively. The UB gives rise to the collecting ducts and lower urinary tract from renal pelvis to a part of urinary bladder, while MM differentiates into nephrons and interstitium by developing embryonic progenitor cells, such as nephron progenitors (NPs). We have recently established highly efficient differentiation methods from hiPSCs/ESCs into Woffian duct epithelia and NPs through anterior and posterior IMs, respectively. Furthermore, we succeeded in the generation of nephron- and UB-like structures from the induced progenitor cells. We are currently establishing the recombination of these organoids in order to generate functional kidney tissues and to create the disease models from patient-derived hiPSCs. I would like to show our recent efforts towards the development of regenerative therapies and disease modeling for kidney diseases.